Search Results (54)

This study examines resistance inheritance to the pyrethroid insecticides esfenvalerate and deltamethrin in a Puerto Rican strain of fall armyworm (FAW), Spodoptera frugiperda, a major global pest of corn. The resistant strain (PPR) showed significantly higher resistance compared to a susceptible strain (SUS), with a 62-fold X-linked and 15-fold autosomal-linked resistance ratio (RR₅₀) for esfenvalerate and deltamethrin, respectively. Resistance was incompletely dominant for both insecticides. Synergist bioassays revealed that detoxification enzymes play a key role in resistance, with PPR exhibiting increased toxicity across all tested synergists, especially with a 12-fold increase when all were combined. Deltamethrin assays confirmed the importance of these enzymes, with a 17-fold increase in PPR toxicity when combined with esterase inhibitors. These findings highlight the complexity of pyrethroid resistance, involving multiple non-target site mechanisms, and suggest that heterozygous individuals could survive in treated crops due to incomplete dominance. The results emphasize the need for diversified pest management strategies, including insecticide rotation, to effectively control FAW populations. Full article

Background: Research has demonstrated that the loss of one or more natural teeth can be an emotionally traumatic experience that mirrors processes associated with bereavement. There remains scant literature examining the role of emotions in dental encounters. One such exception is the literature on the idea of the ‘treatment alliance’ in dental encounters. The aim of this paper is to explore the role of the ‘treatment alliance’ in dentist–patient encounters. Methods: Data were collected from clinical observations, semi-structured interviews and focus groups exploring the experience of tooth loss and how the treatment alliance shaped the patient journey. Data analysis was conducted using the grounded theory method influenced by phenomenology. Coding was conducted using NVIVO and the unit of analysis was the treatment alliance. Results: Twenty participants took part in the interviews (eleven male; nine female; 22–86 years; mean age = 58.9 years). Observations were carried out with a further fourteen participants (seven male; seven female; 50–101 years; mean age = 62.2 years). The paper draws on four cases taken from the observational data to illustrate important dynamics underpinning how the treatment alliance varied. These case studies are then used as the basis for a critical discussion of the importance of the treatment alliance in dentistry. Conclusions: The treatment alliance acted as an important moderator in the clinical encounter, helping to influence successful outcomes. An important foundational component of the treatment alliance was the degree of emotional work the dental team conducted when ‘getting to know’ unfamiliar patients. Whilst emotions were an important factor in dental encounters, their acknowledgement and management were not essential to all successful outcomes. Much more research is therefore needed into the role of emotional labour in dental encounters. Full article

Coarctation of the aorta (CoA) comprises 5–7% of congenital heart disease and can present as an isolated narrowing in the aortic arch just distal to the left subclavian artery or can be associated with cardiac abnormalities such as a bicuspid aortic valve, aortopathy, or ventricular septal defects. With the advances in the medical field, intervention on CoA can either be via surgical repair or endovascular stenting. Echocardiography is the mainstay in diagnosing CoA, with tomographic imaging such as magnetic resonance imaging (MRI) or computed tomography providing supplementary assessment of the aorta, valves, and collateral vessels. We present a case of a young hypertensive male who was noted to have a continuous cardiac murmur with diagnostic Doppler pattern of CoA on echocardiography that normalized soon after percutaneous stenting. Full article

Objectives: In vitro fertilization (IVF) has the potential to give babies to millions more people globally, yet it continues to be underutilized. We established a globally applicable and locally adaptable IVF prognostics report and framework to support patient–provider counseling and enable validated, data-driven treatment decisions. This study investigates the IVF utilization rates associated with the usage of machine learning, center-specific (MLCS) prognostic reports (the Univfy^® report) in provider-patient pre-treatment and IVF counseling. Methods: We used a retrospective cohort comprising 24,238 patients with new patient visits (NPV) from 2016 to 2022 across seven fertility centers in 17 locations in seven US states and Ontario, Canada. We tested the association of Univfy report usage and first intra-uterine insemination (IUI) and/or first IVF usage (a.k.a. conversion) within 180 days, 360 days, and “Ever” of NPV as primary outcomes. Results: Univfy report usage was associated with higher direct IVF conversion (without prior IUI), with odds ratios (OR) 3.13 (95% CI 2.83, 3.46), 2.89 (95% CI 2.63, 3.17), and 2.04 (95% CI 1.90, 2.20) and total IVF conversion (with or without prior IUI), OR 3.41 (95% CI 3.09, 3.75), 3.81 (95% CI 3.49, 4.16), and 2.78 (95% CI 2.59, 2.98) in 180-day, 360-day, and Ever analyses, respectively; p < 0.05. Among patients with Univfy report usage, after accounting for center as a factor, older age was a small yet independent predictor of IVF conversion. Conclusions: Usage of a patient-centric, MLCS-based prognostics report was associated with increased IVF conversion among new fertility patients. Further research to study factors influencing treatment decision making and real-world optimization of patient-centric workflows utilizing the MLCS reports is warranted. Full article

In this study, a mixed porcine–human bioengineered liver (MPH-BEL) was used in a preclinical setup of extracorporeal liver support devices as a treatment for a model of post-resection liver failure (PRLF). The potential for human clinical application is further illustrated by comparing the functional capacity of MPH-BEL grafts as assessed using this porcine PRLF model with fully human (FH-BEL) grafts which were perfused and assessed in vitro. BEL grafts were produced by reseeding liver scaffolds with HUVEC and primary porcine hepatocytes (MPH-BEL) or primary human hepatocytes (FH-BEL). PRLF was induced by performing an 85% liver resection in domestic white pigs and randomized into the following three groups 24 h after resection: standard medical therapy (SMT) alone, SMT + extracorporeal circuit (ECC), and SMT + MPH-BEL. The detoxification and metabolic functions of the MPH-BEL grafts were compared to FH-BEL grafts which were perfused in vitro. During the 24 h treatment interval, INR values normalized within 18 h in the MPH-BEL therapy group and urea synthesis increased as compared to the SMT and SMT + ECC control groups. The MPH-BEL treatment was associated with more rapid decline in hematocrit and platelet count compared to both control groups. Histological analysis demonstrated platelet sequestration in the MPH-BEL grafts, possibly related to immune activation. Significantly higher rates of ammonia clearance and metabolic function were observed in the FH-BEL grafts perfused in vitro than in the MPH-BEL grafts. The MPH-BEL treatment was associated with improved markers of liver function in PRLF. Further improvement in liver function in the BEL grafts was observed by seeding the biomatrix with human hepatocytes. Methods to reduce platelet sequestration within BEL grafts is an area of ongoing research. Full article

Tumor- and treatment-related factors are established predictors of ovarian cancer survival. New studies suggest a differential impact of exposures on ovarian cancer survival trajectories (i.e., rapidly fatal to long-term disease). This study examined the impact of pre-diagnostic risk factors on short- and long-term ovarian cancer survival trajectories in the Canadian context. This population-based longitudinal observational study included women diagnosed with invasive epithelial ovarian cancer from 1995 to 2004 in Ontario. Data were obtained from medical records, interviews, and the provincial cancer registry. Extended Cox proportional hazard models estimated the association between risk factors and all-cause and ovarian cancer-specific mortality by survival time intervals (<3 years (i.e., short-term survival), 3 to <6 years, 6 to <10 years, and ≥10 years (i.e., long-term survival)). Among 1421 women, histology, stage, and residual disease were the most important predictors of all-cause mortality in all survival trajectories, particularly for short-term survival. Reproductive and lifestyle factors did not strongly impact short-term overall survival but were associated with long-term overall survival. As such, among long-term survivors, history of breastfeeding significantly decreased the risk of all-cause mortality (HR 0.65; 95% CI 0.46, 0.93; p < 0.05), whereas smoking history (HR 1.75; 95% CI 1.27, 2.40; p < 0.05) and obesity (HR 1.81; 95% CI 1.24, 2.65; p < 0.05) significantly increased the risk of all-cause mortality. The findings were consistent with ovarian cancer-specific mortality. These findings suggest that pre-diagnostic exposures differentially influence survival time following a diagnosis of ovarian cancer. Full article

Epicardial pulsed field ablation (PFA) of ganglionated plexi (GPs) is being explored as a potential treatment for atrial fibrillation. Initial work using open-chest access with a monopolar ablation device has been completed. This study describes the early development work for a device that can be used with subxiphoid access and deliver bipolar ablation pulses. Electric field computational models have been used for the initial guidance on pulse parameters. An in vivo assessment of these ablation parameters has been performed in an open-chest canine study, while subxiphoid access and navigation of the device has been demonstrated in a porcine model. Results from this acute study have demonstrated the promising potential of this approach. Full article

Endourology occupies an important place in modern urological practice. Compared with conventional surgery, it offers improved safety and patients experience less severe postoperative effects. Its use requires a certain level of equipment and technical skills. In many developed countries, it has been established for years and its practice has become routine. In Africa, it is still not very practical or even non-existent in certain reference centers. This survey conducted among the heads of urology departments or training coordinators in African referral centers defines the current practice of endourology. According to the needs and perspectives identified, it is important, if not essential, to create services or reference centers specializing in endourology. The role of these centers will be to take care of patients and train urologists in technical skills. The creation of a sub-regional and international network could contribute to the development of this practice. Multi-stakeholder cooperation (inter-state, with non-governmental organizations, companies or corporations) is also necessary. Full article

Natural killer (NK) cells play a vital role in xenotransplantation rejection. One approach to induce NK cell immune tolerance is to prevent the NK cell-mediated direct killing of porcine cells by targeting the interaction of the activating receptor NKG2D and its ligands. However, the identity of porcine ligands for the human NKG2D receptor has remained elusive. Previous studies on porcine UL-16 binding protein 1 (pULBP-1) as a ligand for human NKG2D have yielded contradictory results. The goal of the present study was to clarify the role of pULBP-1 in the immune response and its interaction with human NKG2D receptor. To accomplish this, the CRISPR/Cas9 gene editing tool was employed to disrupt the porcine ULBP-1 gene in a 5-gene knockout porcine endothelial cell line (GGTA1, CMAH, β4galNT2, SLA-I α chain, and β-2 microglobulin, 5GKO). A colony with two allele mutations in pULBP-1 was established as a 6-gene knockout pig cell line (6GKO). We found that pULBP-1-deficient pig cells exhibited a reduced binding capacity to human NKG2D-Fc, a recombinant chimera protein. However, the removal of ULBP-1 from porcine endothelial cells did not significantly impact human NK cell degranulation or cytotoxicity upon stimulation with the pig cells. These findings conclusively demonstrate that pULBP-1 is not a crucial ligand for initiating xenogeneic human NK cell activation. Full article

Acute Liver Failure (ALF) is a life-threatening illness characterized by the rapid onset of abnormal liver biochemistries, coagulopathy, and the development of hepatic encephalopathy. Extracorporeal bioengineered liver (BEL) grafts could offer a bridge therapy to transplant or recovery. The present study describes the manufacture of clinical scale BELs created from decellularized porcine-derived liver extracellular matrix seeded entirely with human cells: human umbilical vein endothelial cells (HUVECs) and primary human liver cells (PHLCs). Decellularized scaffolds seeded entirely with human cells were shown to adhere to stringent sterility and safety guidelines and demonstrated increased functionality when compared to grafts seeded with primary porcine liver cells (PPLCs). BELs with PHLCs were able to clear more ammonia than PPLCs and demonstrated lower perfusion pressures during patency testing. Additionally, to determine the full therapeutic potential of BELs seeded with PHLCs, longer culture periods were assessed to address the logistical constraints associated with manufacturing and transporting a product to a patient. The fully humanized BELs were able to retain their function after cold storage simulating a product transport period. Therefore, this study demonstrates the manufacture of bioengineered liver grafts and their potential in the clinical setting as a treatment for ALF. Full article

The evolutionary paths of social-ecological systems comprise periods of structural continuity punctuated by moments of convulsive change. Various forms of systemic global shock could materialize in the coming decades, triggered by the climate crisis, social disruption, economic breakdown, financial collapse, nuclear conflict, or pandemics. The unfolding COVID-19 pandemic stands as a real-time example of an interruption of historic continuity. More hopefully, deep institutional and cultural shifts could rapidly usher in more resilient forms of global civilization. These plausible possibilities challenge scenario studies to spotlight discontinuous futures, an imperative that has not been adequately met. Several factors—for example, gradualist theories of change, scientific reticence, the lure of quantitative tractability, embeddedness in policymaking processes—have rendered mainstream scenario analysis ill-suited to the task. The emphasis on continuity fails to alert decision makers and the public to the risks and opportunities latent in our singular historical moment. A shift to a paradigm that foregrounds discontinuity is long overdue, calling for efforts to broaden the base of persons involved; devote more attention to balancing narrative storytelling and a broader range of quantitative methods; and apply and develop methods to explicitly consider discontinuities in global scenario development. Full article

Atrial fibrillation (AF) is the most common cardiac arrhythmia affecting millions of people worldwide. The cardiac autonomic nervous system (ANS) is widely recognized as playing a key role in both the initiation and propagation of AF. This paper reviews the background and development of a unique cardioneuroablation technique for the modulation of the cardiac ANS as a potential treatment for AF. The treatment uses pulsed electric field energy to selectively electroporate ANS structures on the epicardial surface of the heart. Insights from in vitro studies and electric field models are presented as well as data from both pre-clinical and early clinical studies. Full article

Purpose: To retrospectively review the clinical outcomes of patients with metastatic breast cancer (MBCa) following liver directed ablative intent radiotherapy (RT). Methods: Demographics, disease and treatment characteristics of patients with MBCa who received liver metastasis (LM) directed ablative RT between 2004–2020 were analysed. The primary outcome was local control (LC), secondary outcomes included overall survival (OS) and progression-free survival (PFS) analyzed by univariate (UVA) and multi-variable analysis (MVA). Results: Thirty MBCa patients with 50 LM treated with 5–10 fraction RT were identified. Median follow-up was 14.6 (range 0.9–156.2) months. Class of metastatic disease was described as induced (12 patients, 40%), repeat (15 patients, 50%) and de novo (three patients, 10%). Median size of treated LM was 3.1 cm (range 1–8.8 cm) and median biologically effective dose delivered was 122 (Q1–Q3; 98–174) Gy₃. One-year LC rate was 100%. One year and two-year survival was 89% and 63%, respectively, with size of treated LM predictive of OS (HR 1.35, p = 0.023) on UVA. Patients with induced OMD had a significantly higher rate of progression (HR 4.77, p = 0.01) on UVA, trending to significance on MVA (HR 3.23, p = 0.051). Conclusions: Hypo-fractionated ablative liver RT in patients with MBCa provides safe, tolerable treatment with excellent LC. Full article

Background: Post-transcatheter aortic valve replacement (TAVR) patient outcome is an important research topic. To accurately assess post-TAVR mortality, we examined a family of new echo parameters (augmented systolic blood pressure (AugSBP) and arterial mean pressure (AugMAP)) derived from blood pressure and aortic valve gradients. Methods: Patients in the Mayo Clinic National Cardiovascular Diseases Registry-TAVR database who underwent TAVR between 1 January 2012 and 30 June 2017 were identified to retrieve baseline clinical, echocardiographic and mortality data. AugSBP, AugMAP and valvulo-arterial impedance (Zva) (Zva) were evaluated using Cox regression. Receiver operating characteristic curve analysis and the c-index were used to assess the model performance against the Society of Thoracic Surgeons (STS) risk score. Results: The final cohort contained 974 patients with a mean age of 81.4 ± 8.3 years old, and 56.6% were male. The mean STS risk score was 8.2 ± 5.2. The median follow-up duration was 354 days, and the one-year all-cause mortality rate was 14.2%. Both univariate and multivariate Cox regression showed that AugSBP and AugMAP parameters were independent predictors for intermediate-term post-TAVR mortality (all p < 0.0001). AugMAP1 < 102.5 mmHg was associated with a 3-fold-increased risk of all-cause mortality 1-year post-TAVR (hazard ratio 3.0, 95%confidence interval 2.0–4.5, p < 0.0001). A univariate model of AugMAP1 surpassed the STS score model in predicting intermediate-term post-TAVR mortality (area under the curve: 0.700 vs. 0.587, p = 0.005; c-index: 0.681 vs. 0.585, p = 0.001). Conclusions: Augmented mean arterial pressure provides clinicians with a simple but effective approach to quickly identify patients at risk and potentially improve post-TAVR prognosis. Full article

Human papillomavirus (HPV) infection has been identified as a significant etiological agent in the development of head and neck squamous cell carcinoma (HNSCC). HPV’s involvement has alluded to better survival and prognosis in patients and suggests that different treatment strategies may be appropriate for them. Only some data on the epidemiology of HPV infection in the oropharyngeal, oral cavity, and laryngeal SCC exists in Europe. Thus, this study was carried out to investigate HPV’s impact on HNSCC patient outcomes in the Irish population, one of the largest studies of its kind using consistent HPV testing techniques. A total of 861 primary oropharyngeal, oral cavity, and laryngeal SCC (OPSCC, OSCC, LSCC) cases diagnosed between 1994 and 2013, identified through the National Cancer Registry of Ireland (NCRI), were obtained from hospitals across Ireland and tested for HPV DNA using Multiplex PCR Luminex technology based in and sanctioned by the International Agency for Research on Cancer (IARC). Both overall and cancer-specific survival were significantly improved amongst all HPV-positive patients together, though HPV status was only a significant predictor of survival in the oropharynx. Amongst HPV-positive patients in the oropharynx, surgery alone was associated with prolonged survival, alluding to the potential for de-escalation of treatment in HPV-related OPSCC in particular. Cumulatively, these findings highlight the need for continued investigation into treatment pathways for HPV-related OPSCC, the relevance of introducing boys into national HPV vaccination programs, and the relevance of the nona-valent Gardasil-9 vaccine to HNSCC prevention. Full article